Hydrogels are materials that absorb solvents (such as water), undergo rapid swelling without discernible dissolution, and maintain three-dimensional networks capable of reversible deformation. See, e.g., Park, et al., Biodegradable Hydrogels for Drug Delivery, Technomic Pub. Co., Lancaster, Pa. (1993).
Hydrogels may be uncrosslinked or crosslinked. Uncrosslinked hydrogels are able to absorb water but do not dissolve due to the presence of hydrophobic and hydrophilic regions. A number of investigators have explored the concept of combining hydrophilic and hydrophobic polymeric components in block (Okano, et al., “Effect of hydrophilic and hydrophobic microdomains on mode of interaction between block polymer and blood platelets”, J. Biomed. Mat. Research, 15:393-402 (1981), or graft copolymeric structures (Onishi, et al., in Contemporary Topics in Polymer Science, (Bailey & Tsuruta, Eds.), Plenum Pub. Co., New York, 1984, p. 149), and blends (Shah, “Novel two-phase polymer system,” Polymer, 28:1212-1216 (1987) and U.S. Pat. No. 4,369,229 to Shah) to form the “hydrophobic-hydrophilic” domain systems, which are suited for thermoplastic processing. See, Shah, Chap. 30, in Water Soluble Polymers (Shalaby et al., Eds.), Vol. 467, ACS-Symp. Ser., Amer. Chem. Soc., Washington (1991). These uncrosslinked materials can form hydrogels when placed in an aqueous environment.
Hydrogels may be formed by physical or chemical crosslinking, or a combination of these two processes. Physical crosslinking takes place as a result of ionic linkages, hydrogen bonding, Van der Waals forces, or other such physical forces. Chemical crosslinking occurs due to the formation of covalent linkages. Covalently crosslinked networks of hydrophilic polymers, including water-soluble polymers are traditionally denoted as hydrogels (or aquagels) in the hydrated state. Hydrogels have been prepared based on crosslinked polymeric chains of methoxypoly(ethylene glycol) monomethacrylate having variable lengths of the polyoxyethylene side chains, and their interaction with blood components has been studied (Nagaoka et al., in Polymers as Biomaterial (Shalaby et al., Eds.) Plenum Press, 1983, p. 381). A number of aqueous hydrogels have been used in various biomedical applications, such as, for example, soft contact lenses, wound management, and drug delivery.
The concept of injecting hydrogels to fill spaces or tracks is described in U.S. Pat. No. 5,645,583 to Villain et al. That patent describes a polyethylene oxide gel implant that may be injected into a human body for tissue replacement and augmentation. U.S. Pat. No. 5,090,955 to Simon describes the use of gels in ophthalmology for corneal tissue augmentation procedures such as Gel Injection Adjustable Keratoplasty (GIAK). Neither patent mentions of augmentation of such tissue by hydration and swelling-induced shape changes in the tissue. Instead, for example, the Simon patent describes “smoothing and massaging” of the cornea to remove excess hydrogel material.
Non-degradable hydrogels made from poly(vinyl pyrrolidone) and methacrylate have been fashioned into fallopian tubal occluding devices that swell and occlude the lumen of the tube. See, Brundin, “Hydrogel tubal blocking device: P-Block”, in Female Transcervical Sterilization, (Zatuchini et al., Eds.) Harper Row, Philadelphia (1982), pp. 240-244. Because such hydrogels undergo a relatively small amount of swelling and are not absorbable, so that the sterilization is not reversible, the devices described in the foregoing reference have found limited utility.
U.S. Pat. No. 5,324,775 to Rhee et al. describes injectable particles based on swellable natural polymers that may be suspended in a non-aqueous fluid, e.g., an oil. The particles are formed from ground solid articles and may be injected into soft tissue to rehydrate in-situ to augment the tissue. A significant drawback of the compositions described in that patent, however, is the requirement that a non-aqueous and water insoluble carrier be used to inject the particles.
In view of the foregoing, it would be desirable to provide methods of using hydrogel materials, for example, for temporary occlusion of a body lumen or for tissue augmentation, that overcome the drawbacks of previously known compositions and methods.
It therefore would be desirable to provide methods of forming and using medically useful articles that comprise absorbable hydrogels, capable of undergoing a relatively large degree of swelling in-situ.
In addition to tissue augmentation and lumen occlusion, absorbable hydrogel articles may have application in sealing surgically created voids. For example, tissue biopsy is a very commonly performed minor surgical procedure, and is often to confirm or rule out the presence of disease that has been identified by a previously undertaken diagnostic modality, e.g., X-rays or ultrasound imaging.
Often needle biopsies are performed on solid organs using needles that are introduced from the outside of the patient's body, across the pelvic or thoracic wall. Visualization in performing such procedures is typically limited and the cutting action of the needle often generates associated complications subsequent to the biopsy. Increasing experience with percutaneous biopsy has clarified some subtle points and controversies about possible complications and their prevention.
For example, while hemorrhage is possible with even the smallest aspiration needle, the risk has generally been assumed to increase significantly with the use of larger cutting needles and/or in patients with coagulation deficiencies. Some argue that the benefits attained with the use of cutting needles therefore is not worth the added risk. Unfortunately, while fine-needle aspiration techniques may provide the necessary tissue for cytologic diagnosis in many cases, there are situations in which cutting needles are needed for optimal diagnostic accuracy, such as biopsy of the retroperitoneum (when lymphoma is likely and must be typed) and in the diagnosis of unusual neoplasms, benign neoplasms, or diffuse hepatic or renal parenchymal diseases.
Even though needle biopsy is widely regarded as safe, often times leaks may develop in the underlying tissues due to the needle puncture. For example, when conducting a needle biopsy of the lung, air leaks may develop, leading to collapse of the lung and/or pneumothorax. The incidence of clinically significant pneumothorax following needle biopsy has been reported to be in the 15-25% range. Needle biopsy also is used to assess whether kidney transplantation has been successful, and is associated with the formation of arteriovenous fistulae in 10-15% of cases. Likewise, biopsy of the liver and spleen lead to bleeding complications in 5-10% of cases.
Liver biopsy is essential to the management of liver diseases. Although generally safe, the presence of a vascular tumor, bleeding diathesis or ascites makes the procedure more hazardous. The development of transvenous hepatic biopsy techniques have been one response to this problem. Prevention of hemorrhagic complications in high-risk patients has been accomplished with different clinical methods, and with varying degrees of success. Several authors have suggested use of a transjugular route for biopsy of the liver in high-risk patients. More recently, others have suggested that cutting needles may be used in conjunction with various methods to plug the needle track, for example, with steel embolization coils or gelatin sponge particles, such as GELFOAM®, manufactured by Upjohn, Inc., Kalamazoo, Mich.
U.S. Pat. No. 5,522,898 to Bao describes a closure device for the repair of skin tissue, controlling bleeding, and reducing the likelihood of inducing excess scar tissue during a routine skin biopsy procedure, using a cylindrical tube made from a foam material which is absorbed in a biopsy site with little tissue reaction. That patent also describes the use of GELFOAM® for topical applications. While GELFOAM® may be effective in preventing bleeding, the sponge has a particulate structure, and is difficult to inject smoothly down a needle track. The risk of clumping and the subsequent scarcity of sponge along the needle track presents a risk of bleeding after non-uniform embolization.
Chisholm et al., in “Fibrin Sealant as a Plug for the Post Liver Biopsy Needle Track,” Clinical Radiology, 40:627-628 (1989) propose the use of fibrin sealants to embolize a needle track. A drawback of this technique, however, is that fibrin sealants are associated with a theoretical risk of disease transmission due to the human and animal proteins that are the constituents of fibrin sealants.
Needle biopsies of other parenchymal tissues, such as kidney or lung tissue, also often result in prolonged hemorrhage or airleak from the site of the biopsy. This especially may present a problem when multiple biopsies are to be obtained from a particular organ.
It therefore would be desirable to provide hydrogel articles and methods for plugging voids created in tissue during surgical procedures, such as a needle track created during a biopsy, so as to reduce the risk of hemorrhage after tissue removal.
Abusafieh et al., in “Development of Self-Anchoring Bone Implants. I. Processing and Material Characterization,” J. Biomed Mater Res., 38:314-327 (1997) describe the development of a self anchoring bone implant formed by polymerizing hydrogels around carbon and KEVLAR® fibers, a registered trademark of E.I. DuPont de Nemours, Inc., Wilmington, Del. The concept of self-anchoring swelling-type orthopedic implants is described by Greenberg et al. in “Stimulation of Bone Formation by a Swelling Endosseous Implant,” J. Biomed Mater Res., 12:922-933 (1978). Such implants would, in principle, dilate in a controlled manner by absorption of body fluids to achieve fixation by an expansion-fit mechanism.
Although research on swelling-type bone implants began more than 15 years ago, exploitation of this concept has been largely hampered by the inability to produce a material with the desired hydromechanical properties. None of the previously known materials are made from absorbable hydrogels and all are essentially permanent implants. Also, because there is a degradation in mechanical properties that accompanies swelling, hydration for such materials has been restricted to less than 5-8% by weight and takes place over long periods of time (several days). Since these previous known implants were intended for load bearing applications, low hydration rates clearly were undesirable.
It therefore also would be desirable to provide methods of using and forming hydrogel articles that hydrate relatively quickly, and without substantial degradation of mechanical properties.